Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals, including humans, as a neurotransmitter—a chemical message released by nerve cells to send signals to other cells [neurons, muscle cells, and gland cells].[1] Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Parts in the body that use or are affected by acetylcholine are referred to as cholinergic. Substances that interfere with acetylcholine activity are called anticholinergics.
Acetylcholine is the neurotransmitter used at the neuromuscular junction—in other words, it is the chemical that motor neurons of the nervous system release in order to activate muscles. This property means that drugs that affect cholinergic systems can have very dangerous effects ranging from paralysis to convulsions. Acetylcholine is also a neurotransmitter in the autonomic nervous system, both as an internal transmitter for the sympathetic nervous system and as the final product released by the parasympathetic nervous system.[1]

The Acetylcholine (ACh), has also been traced in cells of non-neural origins and microbes. Recently, enzymes related to its synthesis, degradation and cellular uptake have been traced back to early origins of unicellular eukaryotes.[2] The protist pathogen Acanthamoeba spp. has shown the presence of ACh, which provides growth and proliferative signals via a membrane located M1-muscarinic receptor homolog.[3]
In the brain, acetylcholine functions as a neurotransmitter and as a neuromodulator. The brain contains a number of cholinergic areas, each with distinct functions; such as playing an important role in arousal, attention, memory and motivation.

Partly because of its muscle-activating function, but also because of its functions in the autonomic nervous system and brain, a large number of important drugs exert their effects by altering cholinergic transmission. Numerous venoms and toxins produced by plants, animals, and bacteria, as well as chemical nerve agents such as Sarin, cause harm by inactivating or hyperactivating muscles via their influences on the neuromuscular junction. Drugs that act on muscarinic acetylcholine receptors, such as atropine, can be poisonous in large quantities, but in smaller doses they are commonly used to treat certain heart conditions and eye problems. Scopolamine, which acts mainly on muscarinic receptors in the brain, can cause delirium and amnesia. The addictive qualities of nicotine are derived from its effects on nicotinic acetylcholine receptors in the brain.

Acetylcholine is a choline molecule that has been acetylated at the oxygen atom. Because of the presence of a highly polar, charged ammonium group, acetylcholine does not penetrate lipid membranes. Because of this, when the drug is introduced externally, it remains in the extracellular space and does not pass through the blood–brain barrier. A synonym of this drug is miochol.

Acetylcholine is synthesized in certain neurons by the enzymecholine acetyltransferase from the compounds choline and acetyl-CoA. Cholinergic neurons are capable of producing ACh. An example of a central cholinergic area is the nucleus basalis of Meynert in the basal forebrain.[4][5]
The enzyme acetylcholinesterase converts acetylcholine into the inactive metabolitescholine and acetate. This enzyme is abundant in the synaptic cleft, and its role in rapidly clearing free acetylcholine from the synapse is essential for proper muscle function. Certain neurotoxins work by inhibiting acetylcholinesterase, thus leading to excess acetylcholine at the neuromuscular junction, causing paralysis of the muscles needed for breathing and stopping the beating of the heart.

Acetylcholine processing in a synapse. After release acetylcholine is broken down by the enzyme acetylcholinesterase.

Like many other biologically active substances, acetylcholine exerts its effects by binding to and activating receptors located on the surface of cells. There are two main classes of acetylcholine receptor, nicotinic and muscarinic. They are named for chemicals that can selectively activate each type of receptor without activating the other: muscarine is a compound found in the mushroom Amanita muscaria; nicotine is found in tobacco.

Nicotinic acetylcholine receptors are ligand-gated ion channels permeable to sodium, potassium, and calcium ions. In other words, they are ion channels embedded in cell membranes, capable of switching from a closed to an open state when acetylcholine binds to them; in the open state they allow ions to pass through. Nicotinic receptors come in two main types, known as muscle-type and neuronal-type. The muscle-type can be selectively blocked by curare, the neuronal-type by hexamethonium. The main location of muscle-type receptors is on muscle cells, as described in more detail below. Neuronal-type receptors are located in autonomic ganglia (both sympathetic and parasympathetic), and in the central nervous system.

Muscarinic acetylcholine receptors have a more complex mechanism, and affect target cells over a longer time frame. In mammals, five subtypes of muscarinic receptors have been identified, labeled M1 through M5. All of them function as G protein-coupled receptors, meaning that they exert their effects via a second messenger system. The M1, M3, and M5 subtypes are Gq-coupled; they increase intracellular levels of IP3 and calcium by activating phospholipase C. Their effect on target cells is usually excitatory. The M2 and M4 subtypes are Gi/Go-coupled; they decrease intracellular levels of cAMP by inhibiting adenylate cyclase. Their effect on target cells is usually inhibitory. Muscarinic acetylcholine receptors are found in both the central nervous system and the peripheral nervous system of the heart, lungs, upper gastrointestinal tract, and sweat glands.

Muscles contract when they receive signals from motor neurons. The neuromuscular junction is the site of the signal exchange. The steps of this process in vertebrates occur as follows: (1) The action potential reaches the axon terminal. (2) Calcium ions flow into the axon terminal. (3) Acetylcholine is released into the synaptic cleft. (4) Acetylcholine binds to postsynaptic receptors. (5) This binding causes ion channels to open and allows sodium ions to flow into the muscle cell. (6) The flow of sodium ions across the membrane into the muscle cell generates an action potential which induces muscle contraction. Labels: A: Motor neuron axon B: Axon terminal C: Synaptic cleft D: Muscle cell E: Part of a Myofibril

Acetylcholine is the substance the nervous system uses to activate skeletal muscles, a kind of striated muscle. These are the muscles used for all types of voluntary movement, in contrast to smooth muscle tissue, which is involved in a range of involuntary activities such as movement of food through the gastrointestinal tract and constriction of blood vessels. Skeletal muscles are directly controlled by motor neurons located in the spinal cord or, in a few cases, the brainstem. These motor neurons send their axons through motor nerves, from which they emerge to connect to muscle fibers at a special type of synapse called the neuromuscular junction.

When a motor neuron generates an action potential, it travels rapidly along the nerve until it reaches the neuromuscular junction, where it initiates an electrochemical process that causes acetylcholine to be released into the space between the presynaptic terminal and the muscle fiber. The acetylcholine molecules then bind to nicotinic ion-channel receptors on the muscle cell membrane, causing the ion channels to open. Sodium ions then flow into the muscle cell, initiating a sequence of steps that finally produce muscle contraction.

The autonomic nervous system controls a wide range of involuntary and unconscious body functions. Its main branches are the sympathetic nervous system and parasympathetic nervous system. Broadly speaking, the function of the sympathetic nervous system is to mobilize the body for action; the phrase often invoked to describe it is fight-or-flight. The function of the parasympathetic nervous system is to put the body in a state conducive to rest, regeneration, digestion, and reproduction; the phrase often invoked to describe it is "rest and digest" or "feed and breed". Both of these aforementioned systems use acetylcholine, but in different ways.

At a schematic level, the sympathetic and parasympathetic nervous systems are both organized in essentially the same way: preganglionic neurons in the central nervous system send projections to neurons located in autonomic ganglia, which send output projections to virtually every tissue of the body. In both branches the internal connections, the projections from the central nervous system to the autonomic ganglia, use acetylcholine as a neurotransmitter to innervate (or excite) cholinergic neurons (neurons expressing nicotinic acetylcholine receptors). In the parasympathetic nervous system the output connections, the projections from ganglion neurons to tissues that don't belong to the nervous system, also release acetylcholine but act on muscarinic receptors. In the sympathetic nervous system the output connections mainly release noradrenaline, although acetylcholine is released at a few points, such as the sudomotor innervation of the sweat glands.

In the central nervous system, ACh has a variety of effects on plasticity, arousal and reward. ACh has an important role in the enhancement of alertness when we wake up,[8] in sustaining attention [9] and in learning and memory.[10]

Damage to the cholinergic (acetylcholine-producing) system in the brain has been shown to be associated with the memory deficits associated with Alzheimer's disease.[11] ACh has also been shown to promote REM sleep.[12]

In addition, ACh acts as an important internal transmitter in the striatum, which is part of the basal ganglia. It is released by cholinergic interneurons. In humans, non-human primates and rodents, these interneurons respond to salient environmental stimuli with responses that are temporally aligned with the responses of dopaminergic neurons of the substantia nigra.[15][16]

Acetylcholine has been implicated in learning and memory in several ways. The anticholinergic drug, scopolamine, impairs acquisition of new information in humans[17] and animals.[10] In animals, disruption of the supply of acetylcholine to the neocortex impairs the learning of simple discrimination tasks, comparable to the acquisition of factual information[18] and disruption of the supply of acetylcholine to the hippocampus and adjacent cortical areas produces forgetting comparable to anterograde amnesia in humans.[19]

The disease myasthenia gravis, characterized by muscle weakness and fatigue, occurs when the body inappropriately produces antibodies against acetylcholine nicotinic receptors, and thus inhibits proper acetylcholine signal transmission. Over time, the motor end plate is destroyed. Drugs that competitively inhibit acetylcholinesterase (e.g., neostigmine, physostigmine, or primarily pyridostigmine) are effective in treating this disorder. They allow endogenously released acetylcholine more time to interact with its respective receptor before being inactivated by acetylcholinesterase in the synaptic cleft (the space between nerve and muscle).

Blocking, hindering or mimicking the action of acetylcholine has many uses in medicine. Drugs acting on the acetylcholine system are either agonists to the receptors, stimulating the system, or antagonists, inhibiting it. Acetylcholine receptor agonists and antagonists can either have an effect directly on the receptors or exert their effects indirectly, e.g., by affecting the enzyme acetylcholinesterase, which degrades the receptor ligand. Agonists increase the level of receptor activation, antagonists reduce it.

Acetylcholine itself does not have therapeutic value as a drug for intravenous administration because of its multi-faceted action(non-selective) and rapid inactivation by cholinesterase. However, it is used in the form of eye drops to cause constriction of the pupil during cataract surgery, which facilitates quick post-operational recovery.

Nicotine binds to and activates nicotinic acetylcholine receptors, mimicking the effect of acetylcholine at these receptors. When ACh interacts with a nicotinic ACh receptor, it opens a Na+ channel and Na+ ions flow into the membrane. This causes a depolarization, and results in an excitatory post-synaptic potential. Thus, ACh is excitatory on skeletal muscle; the electrical response is fast and short-lived.

Many ACh receptor agonists work indirectly by inhibiting the enzyme acetylcholinesterase. The resulting accumulation of acetylcholine causes continuous stimulation of the muscles, glands, and central nervous system, which can result in fatal convulsions if the dose is high.

Organic mercurial compounds, such as methylmercury, have a high affinity for sulfhydryl groups, which causes dysfunction of the enzyme choline acetyltransferase. This inhibition may lead to acetylcholine deficiency, and can have consequences on motor function.

Acetylcholine is used by organisms in all domains of life for a variety of purposes. It is believed that choline, a precursor to acetylcholine, was used by single celled organisms billions of years ago[2] for synthesizing cell membrane phospholipids.[20] Following the evolution of choline transporters, the abundance of intracellular choline paved the way for choline to become incorporated into other synthetic pathways, including acetylcholine production. Acetylcholine is used by bacteria, fungi, and a variety of other animals. Many of the uses of acetylcholine rely on its action on ion channels via GPCRs like membrane proteins[3].

The two major types of acetylcholine receptors, muscarinic and nicotinic receptors, have convergently evolved to be responsive to acetylcholine. This means that rather than having evolved from a common homolog, these receptors evolved from separate receptor families. It is estimated that the nicotinic receptor family dates back longer than 2.5 billion years.[20] Likewise, muscarinic receptors are thought to have diverged from other GPCRs at least 0.5 billion years ago. Both of these receptor groups have evolved numerous subtypes with unique ligand affinities and signaling mechanisms. The diversity of the receptor types enables acetylcholine to creating varying responses depending on which receptor types are activated, and allow for acetylcholine to dynamically regulate physiological processes.

1.
Oxygen
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Oxygen is a chemical element with symbol O and atomic number 8. It is a member of the group on the periodic table and is a highly reactive nonmetal. By mass, oxygen is the third-most abundant element in the universe, after hydrogen, at standard temperature and pressure, two atoms of the element bind to form dioxygen, a colorless and odorless diatomic gas with the formula O2. This is an important part of the atmosphere and diatomic oxygen gas constitutes 20. 8% of the Earths atmosphere, additionally, as oxides the element makes up almost half of the Earths crust. Most of the mass of living organisms is oxygen as a component of water, conversely, oxygen is continuously replenished by photosynthesis, which uses the energy of sunlight to produce oxygen from water and carbon dioxide. Oxygen is too reactive to remain a free element in air without being continuously replenished by the photosynthetic action of living organisms. Another form of oxygen, ozone, strongly absorbs ultraviolet UVB radiation, but ozone is a pollutant near the surface where it is a by-product of smog. At low earth orbit altitudes, sufficient atomic oxygen is present to cause corrosion of spacecraft, the name oxygen was coined in 1777 by Antoine Lavoisier, whose experiments with oxygen helped to discredit the then-popular phlogiston theory of combustion and corrosion. One of the first known experiments on the relationship between combustion and air was conducted by the 2nd century BCE Greek writer on mechanics, Philo of Byzantium. In his work Pneumatica, Philo observed that inverting a vessel over a burning candle, Philo incorrectly surmised that parts of the air in the vessel were converted into the classical element fire and thus were able to escape through pores in the glass. Many centuries later Leonardo da Vinci built on Philos work by observing that a portion of air is consumed during combustion and respiration, Oxygen was discovered by the Polish alchemist Sendivogius, who considered it the philosophers stone. In the late 17th century, Robert Boyle proved that air is necessary for combustion, English chemist John Mayow refined this work by showing that fire requires only a part of air that he called spiritus nitroaereus. From this he surmised that nitroaereus is consumed in both respiration and combustion, Mayow observed that antimony increased in weight when heated, and inferred that the nitroaereus must have combined with it. Accounts of these and other experiments and ideas were published in 1668 in his work Tractatus duo in the tract De respiratione. Robert Hooke, Ole Borch, Mikhail Lomonosov, and Pierre Bayen all produced oxygen in experiments in the 17th and the 18th century but none of them recognized it as a chemical element. This may have been in part due to the prevalence of the philosophy of combustion and corrosion called the phlogiston theory, which was then the favored explanation of those processes. Established in 1667 by the German alchemist J. J. Becher, one part, called phlogiston, was given off when the substance containing it was burned, while the dephlogisticated part was thought to be its true form, or calx. The fact that a substance like wood gains overall weight in burning was hidden by the buoyancy of the combustion products

2.
Tissue (biology)
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In biology, tissue is a cellular organizational level intermediate between cells and a complete organ. A tissue is an ensemble of similar cells from the origin that together carry out a specific function. Organs are then formed by the grouping together of multiple tissues. The study of tissue is known as histology or, in connection with disease, the classical tools for studying tissues are the paraffin block in which tissue is embedded and then sectioned, the histological stain, and the optical microscope. In the last couple of decades, developments in microscopy, immunofluorescence. With these tools, the appearances of tissues can be examined in health and disease. Animal tissues are grouped into four types, connective, muscle, nervous. Collections of tissues joined in structural units to serve a common function compose organs, while all animals can generally be considered to contain the four tissue types, the manifestation of these tissues can differ depending on the type of organism. For example, the origin of the cells comprising a particular type may differ developmentally for different classifications of animals. By contrast, a true epithelial tissue is present only in a layer of cells held together via occluding junctions called tight junctions. This tissue covers all surfaces that come in contact with the external environment such as the skin, the airways. It serves functions of protection, secretion, and absorption, and is separated from other tissues below by a basal lamina and they are made up of cells separated by non-living material, which is called an extracellular matrix. This matrix can be liquid or rigid, for example, blood contains plasma as its matrix and bones matrix is rigid. Connective tissue gives shape to organs and holds them in place, blood, bone, tendon, ligament, adipose and areolar tissues are examples of connective tissues. One method of classifying tissues is to divide them into three types, fibrous connective tissue, skeletal connective tissue, and fluid connective tissue. Muscle cells form the active contractile tissue of the known as muscle tissue or muscular tissue. Muscle tissue functions to force and cause motion, either locomotion or movement within internal organs. Cells comprising the nervous system and peripheral nervous system are classified as nervous tissue

3.
Biosynthesis
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Biosynthesis is a multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms. In biosynthesis, simple compounds are modified, converted into other compounds and this process often consists of metabolic pathways. Some of these pathways are located within a single cellular organelle, while others involve enzymes that are located within multiple cellular organelles. Examples of these pathways include the production of lipid membrane components. The prerequisite elements for biosynthesis include, precursor compounds, chemical energy and these elements create monomers, the building blocks for macromolecules. Biosynthesis occurs due to a series of chemical reactions, for these reactions to take place, the following elements are necessary, Precursor compounds, these compounds are the starting molecules or substrates in a reaction. These may also be viewed as the reactants in a chemical process. Chemical energy, chemical energy can be found in the form of high energy molecules and these molecules are required for energetically unfavorable reactions. Furthermore, the hydrolysis of these compounds drives a reaction forward, high energy molecules, such as ATP, have three phosphates. Often, the phosphate is split off during hydrolysis and transferred to another molecule. Catalytic enzymes, these molecules are special proteins that catalyze a reaction by increasing the rate of the reaction, coenzymes or cofactors, cofactors are molecules that assist in chemical reactions. These may be metal ions, vitamin derivatives such as NADH and acetyl CoA, in the case of NADH, the molecule transfers a hydrogen, whereas acetyl CoA transfers an acetyl group, and ATP transfers a phosphate. Two examples of type of reaction occur during the formation of nucleic acids. For some of these steps, chemical energy is required, Precursor molecule + ATP ↽ − − ⇀ product AMP + PP i Simple compounds that are converted into other compounds with the assistance of cofactors. For example, the synthesis of phospholipids requires acetyl CoA, while the synthesis of another component, shingolipids. The general equation for these examples is, Precursor molecule + Cofactor → e n z y m e macromolecule Simple compounds that join together to create a macromolecule, for example, fatty acids join together to form phopspholipids. In turn, phospholipids and cholesterol interact noncovalently in order to form the lipid bilayer and this reaction may be depicted as follows, Molecule 1 + Molecule 2 ⟶ macromolecule Many intricate macromolecules are synthesized in a pattern of simple, repeated structures. For example, the simplest structures of lipids are fatty acids, fatty acids are hydrocarbon derivatives, they contain a carboxyl group “head” and a hydrocarbon chain “tail. ”These fatty acids create larger components, which in turn incorporate noncovalent interactions to form the lipid bilayer

4.
Neuromuscular junction
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A neuromuscular junction is a chemical synapse formed by the contact between a motor neuron and a muscle fiber. It is at the junction that a motor neuron is able to transmit a signal to the muscle fiber. Muscles require innervation to function—and even just to muscle tone. Calcium ions bind to sensor proteins on synaptic vesicles, triggering vesicle fusion with the cell membrane, nAChRs are ionotropic receptors, meaning they serve as ligand-gated ion channels. The binding of ACh to the receptor can depolarize the muscle fiber, neuromuscular junction diseases can be of genetic and autoimmune origin. The neuromuscular junction differs from chemical synapses between neurons, presynaptic motor axons stop 30 nanometers from the sarcolemma, the cell membrane of a muscle cell. This 30-nanometer space forms the synaptic cleft through which signalling molecules are released, the sarcolemma has invaginations called postjunctional folds, which increase the surface area of the membrane exposed to the synaptic cleft. These postjunctional folds form what is referred to as the motor endplate, the presynaptic axons form bulges called terminal boutons that project into the postjunctional folds of the sarcolemma. The presynaptic terminals have active zones that contain vesicles, also called quanta and these vesicles can fuse with the presynaptic membrane and release ACh molecules into the synaptic cleft via exocytosis after depolarization. AChRs are localized opposite the presynaptic terminals by protein scaffolds at the postjunctional folds of the sarcolemma, dystrophin, a structural protein, connects the sarcomere, sarcolemma, and extracellular matrix components. Rapsyn is another protein that docks AChRs and structural proteins to the cytoskeleton, also present is the receptor tyrosine kinase protein MuSK, a signaling protein involved in the development of the neuromuscular junction, which is also held in place by rapsyn. The neuromuscular junction is where a neuron activates a muscle to contract and this influx of Ca2+ causes neurotransmitter-containing vesicles to dock and fuse to the presynaptic neurons cell membrane through SNARE proteins. Fusion of the membrane with the presynaptic cell membrane results in the emptying of the vesicles contents into the synaptic cleft. Acetylcholine diffuses into the cleft and can bind to the nicotinic acetylcholine receptors on the motor endplate. Acetylcholine is a neurotransmitter synthesized from choline and acetyl-CoA, and is involved in the stimulation of muscle tissue in vertebrates as well as in some invertebrate animals. In vertebrate animals, the receptor subtype that is found at the neuromuscular junction of skeletal muscles is the nicotinic acetylcholine receptor. Each subunit of this receptor has a characteristic “cys-loop, ” which is composed of a cysteine residue followed by 13 amino acid residues, the two cysteine residues form a disulfide linkage which results in the “cys-loop” receptor that is capable of binding acetylcholine and other ligands. These cys-loop receptors are only in eukaryotes, but prokaryotes possess ACh receptors with similar properties

5.
Sarin
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Sarin, or GB, is a colorless, odorless liquid, used as a chemical weapon owing to its extreme potency as a nerve agent. It is generally considered a weapon of mass destruction, production and stockpiling of sarin was outlawed as of April 1997 by the Chemical Weapons Convention of 1993, and it is classified as a Schedule 1 substance. In June 1994, the UN Special Commission on Iraqi disarmament destroyed the nerve agent sarin under Security Council resolution 687 concerning the disposal of Iraqs weapons of mass destruction, Sarin is an organophosphorus compound with the formula CH3PF. People who absorb a non-lethal dose, but do not receive medical treatment. Sarin is a molecule because it has four chemically distinct substituents attached to the tetrahedral phosphorus center. The SP form is the active enantiomer due to its greater binding affinity to acetylcholinesterase. The P-F bond is broken by nucleophilic agents, such as water. At high pH, sarin decomposes rapidly to nontoxic phosphonic acid derivatives and it is usually manufactured and weaponized as a racemic mixture—an equal mixture of both enantiomeric forms, as this is a simpler process and provides an adequate weapon. A number of pathways can be used to create sarin. The final reaction typically involves attachment of the group to the phosphorus with an alcoholysis with isopropyl alcohol. Two variants of this process are common and this reaction also gives sarin, but hydrochloric acid as a byproduct instead. The Di-Di process was used by the United States for the production of its unitary sarin stockpile, the scheme below describes an example of Di-Di process. The selection of reagents is arbitrary and reaction conditions and product yield depend on the selected reagents, inert atmosphere and anhydrous conditions are used for synthesis of sarin and other organophosphates. As both reactions leave considerable acid in the product, bulk sarin produced without further treatment has a poor shelf life. Various methods have been tried to resolve these problems, triethylamine was added to UK sarin, with relatively poor success. The Aum Shinrikyo cult experimented with triethylamine as well, N, N-Diethylaniline was used by Aum Shinrikyo for acid reduction. N, N′-Diisopropylcarbodimide was added to sarin produced at Rocky Mountain Arsenal to combat corrosion, isopropylamine was included as part of the M687 155mm field artillery shell, which was a binary sarin weapon system developed by the US Army. Another byproduct of these two processes is diisopropyl methylphosphonate, formed when a second isopropyl alcohol reacts with the sarin itself

6.
Skeletal muscle
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Skeletal muscle is one of three major muscle types, the others being cardiac muscle and smooth muscle. It is a form of striated muscle tissue which is under the control of the somatic nervous system. Most skeletal muscles are attached to bones by bundles of collagen fibers known as tendons, a skeletal muscle refers to multiple bundles of cells called muscle fibers. The fibres and muscles are surrounded by connective tissue layers called fasciae, Muscle fibres, or muscle cells, are formed from the fusion of developmental myoblasts in a process known as myogenesis. Muscle fibres are cylindrical, and have more than one nucleus, Muscle fibers are in turn composed of myofibrils. The myofibrils are composed of actin and myosin filaments, repeated in units called sarcomeres, the sarcomere is responsible for the striated appearance of skeletal muscle, and forms the basic machinery necessary for muscle contraction. Connective tissue is present in all muscles as fascia, Muscle fibres are the individual contractile units within muscle. A single muscle such as the biceps contains many muscle fibres, another group of cells, the myosatellite cells are found between the basement membrane and the sarcolemma of muscle fibers. These cells are normally quiescent but can be activated by exercise or pathology to provide additional myonuclei for muscle growth or repair, development Individual muscle fibers are formed during development from the fusion of several undifferentiated immature cells known as myoblasts into long, cylindrical, multi-nucleated cells. Differentiation into this state is completed before birth with the cells continuing to grow in size thereafter. Microanatomy Skeletal muscle exhibits a distinctive banding pattern when viewed under the due to the arrangement of cytoskeletal elements in the cytoplasm of the muscle fibers. The principal cytoplasmic proteins are myosin and actin which are arranged in a unit called a sarcomere. The interaction of myosin and actin is responsible for muscle contraction, every single organelle and macromolecule of a muscle fiber is arranged to ensure form meets function. The cell membrane is called the sarcolemma with the known as the sarcoplasm. In the sarcoplasm are the myofibrils, the myofibrils are long protein bundles about 1 micrometer in diameter each containing myofilaments. Pressed against the inside of the sarcolemma are the unusual flattened myonuclei, between the myofibrils are the mitochondria. While the muscle fiber does not have a smooth endoplasmic reticulum, the sarcoplasmic reticulum surrounds the myofibrils and holds a reserve of the calcium ions needed to cause a muscle contraction. Periodically, it has dilated end sacs known as terminal cisternae and these cross the muscle fiber from one side to the other

7.
Autonomic nervous system
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The autonomic nervous system is a division of the peripheral nervous system that supplies smooth muscle and glands, and thus influences the function of internal organs. This system is the mechanism in control of the fight-or-flight response. Within the brain, the nervous system is regulated by the hypothalamus. Autonomic functions include control of respiration, cardiac regulation, vasomotor activity and those are then subdivided into other areas and are also linked to ANS subsystems and nervous systems external to the brain. The hypothalamus, just above the stem, acts as an integrator for autonomic functions. The autonomic nervous system has two branches, the nervous system and the parasympathetic nervous system. The sympathetic nervous system is considered the fight or flight system. In many cases, both of these systems have opposite actions where one system activates a response and the other inhibits it. An older simplification of the sympathetic and parasympathetic nervous systems as excitory and inhibitory was overturned due to the many exceptions found, there are inhibitory and excitatory synapses between neurons. Although the ANS is also known as the nervous system. Most autonomous functions are involuntary but they can work in conjunction with the somatic nervous system which provides voluntary control. The autonomic nervous system is divided into the nervous system. The sympathetic division emerges from the cord in the thoracic and lumbar areas. The parasympathetic division has craniosacral “outflow”, meaning that the neurons begin at the cranial nerves, the preganglionic, or first, neuron will begin at the “outflow” and will synapse at the postganglionic, or second, neuron’s cell body. The postganglionic neuron will then synapse at the target organ, the sympathetic nervous system consists of cells with bodies in the lateral grey column from T1 to L2/3. These cell bodies are GVE neurons and are the preganglionic neurons, the parasympathetic nervous system consists of cells with bodies in one of two locations, the brainstem or the sacral spinal cord. These sensory neurons monitor the levels of carbon dioxide, oxygen and sugar in the blood, arterial pressure and they also convey the sense of taste and smell, which, unlike most functions of the ANS, is a conscious perception. Blood oxygen and carbon dioxide are in fact directly sensed by the carotid body, primary sensory neurons project onto “second order” visceral sensory neurons located in the medulla oblongata, forming the nucleus of the solitary tract, that integrates all visceral information

8.
Acetylcholinesterase
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Acetylcholinesterase, also known as AChE or acetylhydrolase, is the primary cholinesterase in the body. It is an enzyme that catalyzes the breakdown of acetylcholine and of some other choline esters that function as neurotransmitters, AChE is found at mainly neuromuscular junctions and in chemical synapses of the cholinergic type, where its activity serves to terminate synaptic transmission. It belongs to family of enzymes. It is the target of inhibition by organophosphorus compounds such as nerve agents. AChE is a hydrolase that hydrolyzes choline esters and it has a very high catalytic activity - each molecule of AChE degrades about 25000 molecules of acetylcholine per second, approaching the limit allowed by diffusion of the substrate. The active site of AChE comprises 2 subsites - the anionic site, the structure and mechanism of action of AChE have been elucidated from the crystal structure of the enzyme. The anionic subsite accommodates the positive quaternary amine of acetylcholine as well as other cationic substrates, the cationic substrates are not bound by a negatively charged amino acid in the anionic site, but by interaction of 14 aromatic residues that line the gorge leading to the active site. All 14 amino acids in the gorge are highly conserved across different species. Among the aromatic amino acids, tryptophan 84 is critical and its substitution with alanine results in a 3000-fold decrease in reactivity, the gorge penetrates half way through the enzyme and is approximately 20 angstroms long. The active site is located 4 angstroms from the bottom of the molecule, the esteratic subsite, where acetylcholine is hydrolyzed to acetate and choline, contains the catalytic triad of three amino acids, serine 200, histidine 440 and glutamate 327. These three amino acids are similar to the triad in other serine proteases except that the glutamate is the third member rather than aspartate, moreover, the triad is of opposite chirality to that of other proteases. The hydrolysis reaction of the ester leads to the formation of an acyl-enzyme. Then, the acyl-enzyme undergoes nucleophilic attack by a molecule, assisted by the histidine 440 group, liberating acetic acid. During neurotransmission, ACh is released from the neuron into the synaptic cleft and binds to ACh receptors on the post-synaptic membrane. AChE, also located on the membrane, terminates the signal transmission by hydrolyzing ACh. The liberated choline is taken up again by the pre-synaptic neuron, a cholinomimetic drug disrupts this process by acting as a cholinergic neurotransmitter that is impervious to acetylcholinesterases lysing action. For a cholinergic neuron to receive another impulse, ACh must be released from the ACh receptor and this occurs only when the concentration of ACh in the synaptic cleft is very low. Inhibition of AChE leads to accumulation of ACh in the synaptic cleft, irreversible inhibitors of AChE may lead to muscular paralysis, convulsions, bronchial constriction, and death by asphyxiation

9.
E number
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E numbers are codes for substances that are permitted to be used as food additives for use within the European Union and Switzerland. Commonly found on labels, their safety assessment and approval are the responsibility of the European Food Safety Authority. Having a single unified list for food additives was first agreed upon in 1962 with food colouring, in 1964, the directives for preservatives were added,1970 for antioxidants and 1974 for the emulsifiers, stabilisers, thickeners and gelling agents. They are increasingly, though rarely, found on North American packaging. In some European countries, E number is used informally as a pejorative term for artificial food additives. This is incorrect, because many components of foods have E numbers, e. g. vitamin C. NB, Not all examples of a fall into the given numeric range. Moreover, many chemicals, particularly in the E400–499 range, have a variety of purposes, the list shows all components that have or had an E-number assigned. Not all additives listed are still allowed in the EU, but are listed as they used to have an E-number, for an overview of currently allowed additives see here. Includes Lists of authorised food additives Food additives database

10.
European Chemicals Agency
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ECHA is the driving force among regulatory authorities in implementing the EUs chemicals legislation. ECHA helps companies to comply with the legislation, advances the safe use of chemicals, provides information on chemicals and it is located in Helsinki, Finland. The Agency, headed by Executive Director Geert Dancet, started working on 1 June 2007, the REACH Regulation requires companies to provide information on the hazards, risks and safe use of chemical substances that they manufacture or import. Companies register this information with ECHA and it is freely available on their website. So far, thousands of the most hazardous and the most commonly used substances have been registered, the information is technical but gives detail on the impact of each chemical on people and the environment. This also gives European consumers the right to ask whether the goods they buy contain dangerous substances. The Classification, Labelling and Packaging Regulation introduces a globally harmonised system for classifying and labelling chemicals into the EU. This worldwide system makes it easier for workers and consumers to know the effects of chemicals, companies need to notify ECHA of the classification and labelling of their chemicals. So far, ECHA has received over 5 million notifications for more than 100000 substances, the information is freely available on their website. Consumers can check chemicals in the products they use, Biocidal products include, for example, insect repellents and disinfectants used in hospitals. The Biocidal Products Regulation ensures that there is information about these products so that consumers can use them safely. ECHA is responsible for implementing the regulation, the law on Prior Informed Consent sets guidelines for the export and import of hazardous chemicals. Through this mechanism, countries due to hazardous chemicals are informed in advance and have the possibility of rejecting their import. Substances that may have effects on human health and the environment are identified as Substances of Very High Concern 1. These are mainly substances which cause cancer, mutation or are toxic to reproduction as well as substances which persist in the body or the environment, other substances considered as SVHCs include, for example, endocrine disrupting chemicals. Companies manufacturing or importing articles containing these substances in a concentration above 0 and they are required to inform users about the presence of the substance and therefore how to use it safely. Consumers have the right to ask the retailer whether these substances are present in the products they buy, once a substance has been officially identified in the EU as being of very high concern, it will be added to a list. This list is available on ECHA’s website and shows consumers and industry which chemicals are identified as SVHCs, Substances placed on the Candidate List can then move to another list

11.
Acetyl chloride
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Acetyl chloride, CH3COCl is an acid chloride derived from acetic acid. It belongs to the class of compounds called acyl halides. It is a colorless, corrosive, volatile liquid, acetyl chloride was first prepared in 1852 by French chemist Charles Gerhardt by reacting potassium acetate with phosphoryl chloride. However, these methods usually gives acetyl chloride contaminated by phosphorus or sulfur impurities, a route avoiding these impurities of phosphorus and sulphur is that of phosgene and acetic acid, COCl2 + CH3COOH = CH3COCl + HCl + CO2. HCl impurities can be removed by distilling the product from dimethylaniline or by degassing the mixture by a stream of argon. When heated, a mixture of acid and acetic acid gives acetyl chloride. It can also be synthesized from the catalytic carbonylation of methyl chloride, acetyl chloride is not expected to exist in nature, because contact with water would hydrolyze it into acetic acid and hydrogen chloride. In fact, if handled in air it releases white smoke resulting from hydrolysis due to the moisture in the air. The smoke is actually small droplets of hydrochloric acid and acetic acid formed by hydrolysis, acetyl chloride is used for acetylation reactions, i. e. the introduction of an acetyl group. Acetyl is a group having the formula-C-CH3. For further information on the types of chemical compounds such as acetyl chloride can undergo. Two major classes of acetylations include esterification and the Friedel-Crafts reaction, acetyl chloride is a reagent for the preparation of esters and amides of acetic acid, used in the derivatization of alcohols and amines. One class of reactions are esterification. Such reactions will often proceed via ketene, a second major class of acetylation reactions are the Friedel-Crafts reactions

A neuromuscular junction (or myoneural junction) is a chemical synapse formed by the contact between a motor neuron and …

At the neuromuscular junction, the nerve fiber is able to transmit a signal to the muscle fiber by releasing ACh (and other substances), causing muscle contraction.

motor endplate

Image: Electron micrograph of neuromuscular junction (cross section)

Muscles will contract or relax when they receive signals from the nervous system. The neuromuscular junction is the site of the signal exchange. The steps of this process in vertebrates occur as follows:(1) The action potential reaches the axon terminal. (2) Voltage-dependent calcium gates open, allowing calcium to enter the axon terminal. (3) Neurotransmitter vesicles fuse with the presynaptic membrane and ACh is released into the synaptic cleft via exocytosis. (4) ACh binds to postsynaptic receptors on the sarcolemma. (5) This binding causes ion channels to open and allows sodium ions to flow across the membrane into the muscle cell. (6) The flow of sodium ions across the membrane into the muscle cell generates an action potential which travels to the myofibril and results in muscle contraction.Labels:A: Motor Neuron AxonB: Axon TerminalC. Synaptic CleftD. Muscle CellE. Part of a Myofibril